Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

Abstract

Aims/hypothesis Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity. Subjects and methods The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n=161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 nonobese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/nondiabetic control subjects (n=1,163). Results Significant association was found for a 5′ variant (rs6857715) in the NPY2R gene with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n=928) vs the control subjects (n=938) (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (codominant model p=0.005, recessive model p=0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family. Conclusions/interpretation These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with Diabetologia (2007)

Lack of Association Between Variants within the AHSG, HCRT and NPY2R Genes and Anthropometrical Parameters in Czech Post-Monica Study

“…The frequencies of the examined genotypes were similar to the previously analyzed populations in AHSG [ 4 , 7 , 8 ] , HCRT [ 18 ] and NPY2R [ 1 , 21 , 23 ] . The number and percentage of individual genotypes and call rates are summarized in Table 3 .…”

“…These abdominal hormones are members of the pancreatic polypeptide family together with pancreatic polypeptide (PP). All these polypeptides have been described as strong central regulators of gastric function [ 1 , 21 ] . Neuropeptide Y is an appetite hormone and is widely distributed throughout the central and peripheral nervous systems.…”

“…Single nucleotide polymorphisms in the NPY2R genes have been found to play a role in obesity, having an additive effect on other genes [ 22 ] . In a study performed on French Caucasians, rs1047214 was selected for genotyping from 12 investigated SNPs [ 21 ] . In accordance with the French and other studies, we decided to investigate this SNP on our database [ 23 ] .…”

Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with a strong family history of type 2 diabetes

“…[16][17][18][19] Unfortunately, PYY secretion was not assessed in these studies, but it is possible that these polymorphisms might lower PYY secretion. These findings support our results and hypothesis that a disturbed PYY release could be part of a primary hereditary defect, promoting the further development of obesity and T2D.…”

Peptide YY (PYY) Gene Polymorphisms in the 3′-Untranslated and Proximal Promoter Regions Regulate Cellular Gene Expression and PYY Secretion and Metabolic Syndrome Traitsin Vivo

“…Ma et al (28) found that obesity was predicted by two PYY genetic variants in Pima Indian men. Siddiq et al (29) found association of an intronic PYY variant with childhood obesity but not in adults in a European sample. However, the mechanism whereby PYY genetic variation influences metabolic syndrome traits has remained elusive.…”